Pallidotomy for Medically Refractory Status Dystonicus in Childhood

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY ORIGINAL ARTICLE

Pallidotomy for medically refractory status dystonicus in childhood

1 Neurosurgery Unit, Department of Neuroscience and Neurorehabilitation, IRCCS Bambino Gesu Children’s Hospital (BGCH), Rome; 2 Department of Neurosurgery, IRCCS Fondazione Istituto Neurologico ‘Carlo Besta’, Milan; 3 Neurorehabilitation Unit, Department of Neuroscience and Neurorehabilitation, IRCCS Bambino Gesu Children’s Hospital (BGCH), Rome; 4 Neurology Unit, Department of Neuroscience and Neurorehabilitation, IRCCS Bambino Gesu Children’s Hospital (BGCH), Rome; 5 Intensive Care Unit, Department of Emergency, IRCCS Bambino Gesu Children’s Hospital (BGCH), Rome, Italy.

Correspondence to Erika Rebessi, Department of Neuroscience and Neurorehabilitation, Neurosurgery Unit, Bambino Gesu Children’s Hospital, IRCCS 4, Piazza Sant’Onofrio, 00165 Rome, Italy. E-mail: [email protected]

This article is commented on by Lumsden on pages 607–608 of this issue.

PUBLICATION DATA AIM Status dystonicus is a rare and potentially fatal condition of continuous and generalized Accepted for publication 29th December muscle contraction that can complicate dystonia. As status dystonicus is usually refractory to 2013. traditional pharmacological therapy, alternative and invasive strategies have been developed, Published online 4th April 2014. but so far there are no guidelines on status dystonicus management. Pallidotomy has shown good results in status dystonicus treatment. ABBREVIATIONS METHOD We report indications, surgical strategy, and outcome of bilateral pallidotomy in BFMDRS Burke-Fahn-Marsden Dystonia four pediatric patients (four males; mean age at surgery 11y 5mo) with secondary dystonia, Rating Scale who developed refractory status dystonicus. Pallidotomy was performed in the area GPi Globus pallidus internus corresponding to the mid portion of the globus pallidus internus. ITB Intrathecal baclofen RESULTS This procedure allowed patients to recover the pre-status dystonicus condition, PEG Percutaneous enteral gastrostomy controlling dystonic postures and movements of trunk and limbs. Moreover oromandibular dystonia, which is resistant to conservative approaches and deep brain stimulation, was signiﬁcantly reduced. No postoperative complications were registered. INTERPRETATION Our study suggests pallidotomy as a feasible treatment in patients with secondary dystonia complicated by status dystonicus.

Dystonia is a clinical syndrome characterized by on status dystonicus showed that surgery appears to be an sustained muscle contraction, frequently causing torsional effective treatment.3 and repetitive movements, or abnormal postures, which The aim of this study was to report indications, surgical can be focal or generalized.1 Dystonia may sporadically strategy, and outcome of bilateral pallidotomy in a series evolve toward a life-threatening condition of severe of four children affected by secondary dystonia who generalized dystonia, called status dystonicus or dystonic developed status dystonicus. storm. Status dystonicus is often triggered by events such as fever, infections, exposure to medications, or their abrupt METHOD cessation. This condition could rapidly lead to rhabdomyol- From March 2011 to January 2012, four pediatric patients ysis, metabolic failure, and bulbar complications, requiring (four males), presenting with severe forms of secondary admission to the intensive care unit (ICU) for sedation and dystonia, were referred to the Department of Neuroscience ventilation.2 Status dystonicus can be refractory to tradi- and Neurorehabilitation of the Bambino Gesu Children’s tional pharmacological therapy. Alternative and invasive Hospital in Rome, which receives tertiary patients for strategies have been developed but no guidelines for status specialist consultations. All patients had an exacerbation of dystonicus management have been unequivocally defined. the disease with status dystonicus, refractory to medical Literature reports reveal that a gradual multistage treatment (Table I), and were prospectively studied. They approach, from enteral pharmacological therapy to ICU fulfilled the diagnostic criteria for status dystonicus procedures and surgery (continuous infusion of intrathecal according to the definition by Manji.2 This includes the baclofen, thalamotomy, pallidotomy, or deep brain stimula- development of increasingly frequent and severe episodes tion) may be required. A recent exhaustive literature report of generalized dystonia necessitating urgent hospital

© 2014 Mac Keith Press DOI: 10.1111/dmcn.12420 649 admission and accompanied by one or more of the follow- What this paper adds ing life-threatening complications: bulbar weakness com- • It reports efficacy of pallidotomy in the management of status dystonicus. promising upper airway patency with the risk of • The mid portion of the globus pallidus internus (GPi) is an effective target in the treatment of status dystonicus. progressive impairment of respiratory function leading to • the development of respiratory failure; exhaustion and Selection of the mid GPi also allows for subsequent pallidal deep brain stimulation of its posteroventral portion. pain; and metabolic imbalances. Selection criteria for bilateral pallidotomy included the Informed consent was given by parents of all four presence of status dystonicus, which was not responsive to patients. Data collection, recording and analysis was per- pharmacological treatment, and associated with a rapid and formed according to our institutional review board and severe decline of clinical conditions (Table I). waiver of consent was obtained for data collection, de- The method used to target the area for pallidotomy was identification and analysis. based on the 3D built volume routinely used in neuronavigation. The technique needs the AC-PC definition to build Surgical treatment the stereotactic volume with the X, Y, and Z coordinates; Pallidotomy was performed, under intravenous general the definition of the globus pallidus internus (GPi) is not anesthesia, by a frameless stereotactic neuronavigation – based on the use of the stereotactic coordinates [18 21mm robotic system (ROSA: RObotized Stereotactic Assistant; laterally, 6mm vertically, and 2mm anteriorly to the inter- Medtech, Newark, NY, USA). The targeted area corre- commissural point to target the posteroventral (VPL) sponding to the mid portion of the GPi, was preoperatively GPi], but on visual direct targeting on magnetic resonance defined by a direct targeting on brain MRI (fast spin echo imaging (MRI) inversion recovery sequences. Afterwards, inversion recovery sequence), and merged with brain CT. the relationship to the mid-commissural point was Microrecording and macrostimulation were performed obtained by the direct targeting that was usually lateral (X) under electromyography (EMG) monitoring to detect the 14 to 18mm, anteroposterior (Y) 3 to 5mm, and vertical nucleus and to exclude the involvement of the pyramidal (Z) 2mm. This target fits with the coordinates used for fibers of the internal capsule by the lesioning. The radio- pallidotomy and with those proposed by other authors for frequency lesion (Cosman RFG-1; Cosman Medical Inc., 4 DBS. Burlington, MA USA) at 40V for 60 second was performed Before the onset of status dystonicus, and before surgery, at the target, 3mm above, and 2mm below it. A second all patients underwent a dystonia assessment including neu- trajectory (2mm posterior, 2mm laterally to the first target) rological evaluation, videotape recording, and the adminis- was used to perform lesioning. tration of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), brain MRI and cranial-computed tomography Case 1 (CT). These clinical and imaging evaluations were The first patient was 15 years old and had started to repeated 1, 3, and 6 months after surgery, and every experience from hypertonia and severe psychomotor delay 6 months thereafter.

Table I: Aetiology and clinical features of the status dystonicus series

Age at Age at status Sex, dystonia dystonicus Precipitating Status dystonicus Case age (y) Diagnosis onset onset (y) factors symptoms Complications

1 M, 15 Chromosomopathy 3y 1st status 1st status dystonicus: Continuous Partial amputation dystonicus: 12 pneumonitis oromandibular, of the tongue 2nd status 2nd status dystonicus: trunk, limbs Pneumonia dystonicus: 13 mononucleosis movements Pain 2 M, 19 Epileptic 1mo 17 Fever Generalized dystonic Renal failure, encephalopathy movements, rhabdomyolysis, opisthotonus, respiratory psychomotor agitation distress Pain 3 M, 6.5 Idiopathic 4mo 5 Enteritis/Ileo-ileal Eyelids clonus, Respiratory bilateral striatal Invagination opisthotonus, distress necrosis upper limbs movements, ﬁxed dystonic posture of the left upper limb 4 M, 12 Severe neonatal 8mo 1st status 1st status dystonicus: Generalized dystonic Severe dysphagia, cerebral hypoxia dystonicus: 8 H1N1 infection movement of eyes, sepsis, deep vein 2nd status 2nd status dystonicus: mouth, head and thrombosis dystonicus: 10 unknown limbs, opisthotonus Pain

650 Developmental Medicine & Child Neurology 2014, 56: 649–656 in the first year of life. Genetic testing displayed a chromo- upper limb tremor, eyelid clonus, opisthotonus, and a fixed somopathy (deletion of the long arm of chromosome 22). dystonic posture of the left upper limb. Two months later, At the age of 3 years, dystonic movements of trunk and during severe enteritis complicated by ileo-ileal invagina- limbs, not responsive to any drugs, associated with spastic tion, a rapid worsening of movement disorder associated tetraplegia appeared. Subsequently, the patient had with loss of head control and environmental contact was frequent respiratory tract infections, and a percutaneous noticed. He was admitted to the ICU and sedated; a PEG enteral gastrostomy (PEG) became necessary because of was also performed. Fifty days from status dystonicus malnutrition. At the age of 12 years, after severe pneumo- onset, a bilateral pallidotomy was carried out. nia, a marked worsening of dystonia occurred, evolving within a week to status dystonicus. The patient was then Case 4 admitted to ICU for sedation and intubation followed by a This 12-year-old patient had a severe hypoxic-ischemic tracheostomy. event at birth, followed by a spastic-dystonic tetraplegia Brain MRI showed a diffuse atrophy, bilaterally involving with mental retardation. At the age of 8 months, general- the cortex and subcortical structures (caudate, putamen, and ized dystonia occurred with axially fixed dystonic postures thalamus). Administration of benzodiazepine, thiopentone, and dystonic movements of the four limbs. Brain MR and phenobarbital, resulted in control of the status dystoni- showed diffuse atrophy involving the basal ganglia. At the cus after a period of 7 months. The patient was then age of 8 years, after an acute respiratory infection caused discharged requiring assisted ventilation during sleep, and by the H1N1 flu virus, the patient had status dystonicus, daily intake of several drugs (clonazepam, tetrabenazine, which caused pain and oxygen desaturation episodes. The baclofen, tizanidine, and phenobarbital). His neurological patient was admitted to the ICU; invasive mechanical ven- condition became stable for 1 year but, after mononucleo- tilation and sedation with midazolam, propofol, and thi- sis, a second episode of status dystonicus occurred with opentone were performed. He underwent an intrathecal severe continuous oromandibular movements causing baclofen (ITB) pump positioning, which halted the status amputation of the tongue. The patient was readmitted to dystonicus. In addition he underwent PEG positioning. the ICU with the same management performed during the Three months after surgery, the ITB system became first status dystonicus. The medical management became infected and was removed. The patient continued to take ineffective and, 2 months after the onset of status dystoni- phenobarbital, baclofen, tetrabenazine, and lorazepam, cus, bilateral pallidotomy was performed. resulting in status dystonicus control. At the age of 10 years, without any apparent provoking factor, he had a Case 2 status dystonicus relapse with clinical features similar to The patient, aged 19 years at the time of writing (May the first episode. A novel ITB pump implantation was 2013), had a diagnosis of epileptic encephalopathy of performed, but it was removed soon after because the unknown etiology in the first year of life. At the age of hardware became infected. A tracheostomy was then 18 months, rapid dyskinetic eye movements, frequent star- performed and several drugs were administrated without tles, episodes of restlessness, and upper limbs dystonic efficacy. The patient developed sepsis and deep vein movements were observed. Rectal diazepam administration thrombosis, and 2 months from status dystonicus onset, a allowed control of dystonia. Because of malnutrition, at bilateral pallidotomy was performed. the age of 14 years, he underwent PEG. Two years later, Medical and surgical management are summarized in the patient had a severe worsening of the dystonic Table II. condition; after an episode of hyperpyrexia, he developed a status dystonicus, refractory to enteral therapy with RESULTS phenobarbital, baclofen, tetrabenazine, and diazepam. The In the series the mean age of dystonia onset was clinical condition was complicated by renal failure with 16.5 months (range 4-36). The mean age at onset of the hypermyoglobinemia, rhabdomyolysis, and respiratory first episode of status dystonicus was 10.8 years (range 5- distress. He was admitted to the ICU of our hospital, but 17); the mean period between status dystonicus onset and deep sedation with midazolam and propofol proved inef- surgery was 46 days (range 14-60). fective and the intubation was followed by a tracheostomy. Neither intraoperative problems nor postoperative At that stage, a bilateral pallidotomy was performed. complications occurred. Mean follow-up after surgery was 18.2 months (range 15-22). All the patients showed Case 3 a progressive improvement of dystonia without any The patient, aged 6 years had a diagnosis of bilateral recurrence of status dystonicus. Resolution of status dystoni- striatal necrosis of unknown aetiology. In the first months cus was obtained within 21 to 60 days after surgery (mean of life, generalized hypertonia was observed, followed by 38). After pallidotomy, dystonic oromandibular, axial and cognitive delay. Cerebrospinal fluid examination revealed a limb postures and movements improved. All the patients low level of homovanilic acid and he started oral therapy recovered to their pre-status dystonicus condition and, at with levodopa, which was partially successful. At the age of the time of writing, they are not restricted to lying in bed 4 years, after a febrile episode, the patient presented with and can spend time in a wheelchair. In patients 1, 2, and

Pallidotomy in Status Dystonicus Carlo Eﬁsio Marras et al. 651 Table II: Treatments performed before pallidotomy

Medical treatment Medical Timing Age at Age at before status treatment of Surgical of PEG tracheostomy Case dystonicus status dystonicus treatment pallidotomy (y) (y)

1 1st status dystonicus: 1st status dystonicus: midazolam, 1st status 60d after 2nd 312 tizanidine, thiopentone, phenobarbital, dystonicus: status risperidone, clonazepam none dystonicus nitrazepam, 2nd status dystonicus: 2nd status onset tetrabenazine, midazolam dystonicus: baclofen, valproic pallidotomy acid, amitriptyline, gabapentin 2nd status dystonicus: tizanidine, nitrazepam tetrabenazine, baclofen, clonazepam, phenobarbital, diazepam 2 Diazepam, Tetrabenazine, baclofen, diazepam, Pallidotomy 14d after status 14 17 lamotrigine, valproic phenobarbital, midazolam, dystonicus acid propofol onset 3 Levodopa Tizanidine, tetrabenazine baclofen, Pallidotomy 50d after status 5 Not performed clonazepam, diazepam, midazolam, dystonicus propofol, thiopentone onset 4 1st status dystonicus: 1st status dystonicus: 1st status 60d after 2nd 810 trazodone, dexamethasone, IG, pimozide, dystonicus: ITB status clonazepam, tetrabenazine, promazine, 2nd status dystonicus baclofen, diazepam, lorazepam, midazolam, propofol, dystonicus: ITB, onset midazolam, thiopentone pallidotomy propofol 2nd status dystonicus: baclofen, 2nd status tetrabenazine, trihexyphenidyl, dystonicus: baclofen, tizanidine, clonazepam phenobarbital, lorazepam, diazepam, baclofen, phenobarbital, clorpromazine, lorazepam, midazolam, propofol, thiopentone, tetrabenazine remifentanil, morphine, ketamine

ITB, intrathecal baclofen; PEG, percutaneous enteral gastrostomy.

4, postoperative dystonia improved compared with the ability to sit in a wheelchair. The BFMDRS severity/dis- pre-status dystonicus dystonia, as shown by reductions in ability scores at the last follow-up were 4/30. the severity scores of the BFMDRS (Table III). At the latest follow-up, all the patients maintained a pharmaco- Case 3 logical politherapy. Status dystonicus was controlled 3 weeks after surgery and dystonic symptoms dramatically improved 30 days later Case 1 (Fig. 1). A further progressive neurological improvement Status dystonicus disappeared with a strong reduction was observed during the 3 months after surgery. Up to of dystonic movements 40 days after surgery. Mild now (15mo after surgery), trunk hyperextension and limbs oromandibular dystonic movements, and sporadic spasms of spasms have disappeared; the patient is able to sit in a right arm and legs, induced by discomfort and pain, wheelchair. After an emotional trigger, smooth dystonic remained. Currently, the patient requires mechanical venti- facial and upper limbs spasms can appear (BFMDRS lation only during the night. At 22 months of follow-up, the severity/disability scores: 57/30). postoperative results are stable (BFMDRS: severity 16, disability 30). Case 4 Resolution of status dystonicus happened 2 months after Case 2 surgery. At the last follow-up (15mo), mild sporadic A progressive improvement of status dystonicus was dystonic movements of the trunk, limbs, and of the oro- observed within 1 month of surgery. Three months after mandibular district, usually aroused by emotional triggers, surgery the patient regained independent respiratory are observed. The patient recovered the capacity for oral function and showed mild dystonic movements of the four feeding and the ability to stay in a wheelchair (BFMDRS limbs. He also recovered environmental contact and the severity/disability scores: 44/26) (Table III).

652 Developmental Medicine & Child Neurology 2014, 56: 649–656 Table III: Early postoperative results and follow-up data

Status dystonicus Drugs at latest outcome after Follow-up BFMDRS before BFMDRS at follow-up Case pallidotomy (mo) status dystonicus latest follow-up (per d)

1 Resolution after 40d 22 Severity: 101/120 Severity: 16/120 Phenobarbital 75mg Disability: 30/30 Disability: 30/30 Tetrabenazine 12mg Tizanidine 8mg Baclofen 26mg Nitrazepam 10mg Clonazepam 0.6mg 2 Resolution after 30d 21 Severity: 84/120 Severity: 4/120 Phenobarbital 100mg Disability: 30/30 Disability: 30/30 Tetrabenazine 50mg Baclofen 75mg Lorazepam 3mg Lamotrigine 63mg Valproic acid 1200mg Ruﬁnamide 900mg 3 Resolution after 21d 15 Severity: 60/120 Severity: 57/120 Tizanidine 12mg Disability: 30/30 Disability: 30/30 Baclofen 10mg Clonazepam 2mg 4 Resolution after 60d 15 Severity: 77/120 Severity: 44/120 Phenobarbital 150mg Disability: 26/30 Disability: 28/30 Clonazepam 2.8mg Lorazepam 4mg Baclofen 50mg

BFMDRS, Burke-Fahn-Marsden Dystonia Rating Scale.

100 ms/D 0.1 mV/D Amp 1 53 Hz

100 ms/D 0.1 mV/D Amp 1

R R R GPi R R R R R Lamina R R R R GPe R R R

Figure 1: Globus pallidus complex activity for various depths (8 to 1mm above the MRI-based target). The top of the figure shows a selected GPifiring recording frame (1s). GPi, globus pallidus internus; GPe global pallidus externus.

At time of induction of general anesthesia, all patients Micro-electrode recording was performed in all four monitored by Bispectral index (BIS) showed a low baseline patients. We analyzed four recording tracks because four value of 60 to 70 because they were still sedated. During out of eight were affected by external electrical ﬁelds. The anesthesia and surgery, BIS was maintained between 35 recordings showed Globus pallidus externus (GPe) ﬁring and 50. The requested time to increase the BIS value to 60 activity 7 to 8mm above the target (frequency discharges to 70 was about 10 minutes. 10 (SD 5Hz), usually followed by a relative decrease in

Pallidotomy in Status Dystonicus Carlo Efisio Marras et al. 653 overall activity corresponding to internal medullary lamina, dystonicus control. In patient 4, ITB permitted control that lies between GPe and GPi. GPi activity was recorded of the first episode of status dystonicus, but it proved at 3 to 2mm to the MRI-based target, with a mean firing ineffective in the status dystonicus relapse. In both discharge rate 35 (SD 10Hz; Fig. 2). circumstances the hardware was removed because of infection. ITB usefulness in the treatment of status dy- DISCUSSION stonicus is questionable, and the rate of complications of Status dystonicus is a rare clinical condition, occurring in ITB, such as catheter site leakage and pump infection, is some dystonic patients. As a result of its infrequence, it is high.6 difficult to define its incidence. It is more commonly Literature data show good results of DBS also in the reported in children with a mean age at onset of 14 years treatment of medical refractory status dystonicus, (SD 9.5).3 sometimes associated with clinical improvement of the Status dystonicus causes pain and exhaustion, can lead to baseline dystonic conditions.7,8 Despite the good results, dehydration, rhabdomyolysis, acute renal failure, respiratory DBS is associated with a complication rate, so-called complications, and is associated with significant mortality. hardware related complications, including infection of the Despite the clinical relevance and the potential disabling DBS system (6.1%), skin erosion (1.3%), lead fracture nature of this disease, neither well-defined management (5%) or migration (5%), pulse generator malfunction, are guidelines nor standardized therapeutic approaches are still more frequently observed in patients with dystonia.9 available. Hardware related complications lead to dystonia This condition is not easily controlled by pharmacologi- worsening and increase the risk of status dystonicus onset – cal therapy alone.2,3 Sedation and tracheal intubation are or recurrence.7,10 12 The incidence of DBS complications the only ways to reach a rapid resolution of spasms or dys- in pediatric patients with status dystonicus may be even tonic movements, thereby avoiding bulbar, respiratory, and higher, considering aspects of soft tissue coverage, subopti- metabolic complications. Further therapeutic strategies, mal nutritional status and prolonged mechanical ventilation including surgery, are sometimes required. In refractory with risk of status dystonicus recurrence and complaint for cases, thalamotomy, pallidotomy, and DBS of the GPi have the patients and their family. Unlike patients with dystonia, been performed with encouraging results.5 those affected by status dystonicus more frequently could In our four pediatric patients, non-invasive procedures, have tracheostomy and PEG with an increased risk of including ICU deep sedation, were ineffective in status hardware related complications.

R L

L R

Vista saggitale Vista coronale

R A P L

L R

Figure 2: Status dystonicus in bilateral striatal necrosis of unknown aetiology (Case 3). On the left, the surgical planning (T1-weighted images with gadolinium: axial, coronal, and sagittal planes); on the right, postoperative MR (T2-weighted images: axial and coronal planes) showing the mid pallidotomy (I: entry point; B target).

654 Developmental Medicine & Child Neurology 2014, 56: 649–656 Lesional procedures, including pallidotomy, represent a is otherwise possible to consider pallidotomy at the VPL viable alternative with several advantages, including a level and a subsequent more anterior DBS. The relationship decreased need for access to specialists and clinical to the mid-commissural point collected in our series by the follow-up, and a lower risk of infection.7 Previous reports direct targeting (lateral X: 14-18mm; anteroposterior Y: reveal that mere unilateral pallidotomy or even unilateral 3-5mm; vertical Z: 2mm) was equivalent to other reported pallidotomy with contralateral GPi-DBS are well tolerated DBS series (anteroposterior 2-6mm; lateral 14-18mm; in the treatment of dystonia.13 Our group previously vertical 2mm). The utility of coordinates with reference described a case of a young patient affected by primary to the mid-commissural point is limited, as has been dystonia, who benefitted from bilateral DBS but required previously reported by the Montpellier group.22 The target device removal after a severe skin erosion. Before the lead definition that we performed was not based on the use of removal, radiofrequency ablation of the GPi was per- the stereotactic coordinates, but on the visual direct target- formed through the DBS electrode resulting in long-term ing on MRI inversion recovery sequences. Moreover our stable control of dystonia.13 Similar results are reached small series is composed of secondary dystonia cases, which both with combination of GPi-DBS and contralateral pal- sometimes show distortion of pallidal boundaries (Fig. 1). lidotomy and bilateral DBS.14 Moreover, pallidotomy Although micro8electrode recording (MER) could reveals its efficacy in patients affected by status dystonicus, increase the risk of hemorrhage, it could also improve both as an independent option.8 A report by Hooper et al. selection of the target and recognition of the surrounding shows different clinical conditions on which lesional structures, so optimizing the clinical response, while mini- procedures are preferred over neuromodulation.14 Whereas mizing adverse effects coming from the involvement of sham-controlled randomized clinical trials are available for internal capsule or optic tract by the lesion.21 bilateral GPi-DBS only, a similar outcome of bilateral pal- Micro8electrode recording and stimulation techniques lidotomy in an open-label retrospective series suggested are well established tools to obtain direct measures of the that pallidotomy is similar to GPi-DBS in effectiveness activity of individual neurons within the basal ganglia, pro- and safety.12 viding relevant insights into the pathophysiology of the Literature data on the frequency of complications in movement disorders,21 which is not completely clear. In a patients who underwent bilateral pallidotomy are discor- recent study, Kojovic et al.23 demonstrated that primary dant: each group referring a different percentage of com- and secondary dystonia have different pathophysiological plications, including speech deterioration and disturbances mechanisms. Pathophysiological deficits in primary dysto- of swallowing and drooling.15,16 nia include reduced inhibition at many levels of the motor Anatomic observations show that the GPi is involved in system and an enhanced cortical plasticity, while a role of both limbic system and extrapyramidal motor control. The cerebellar deficits has been suggested, but has yet to be motor part is represented by the posterior half of the clarified. Pathological mechanisms of secondary dystonia nucleus, the lymbic part corresponds to the anterior are not clear: a reduced intracortical inhibition has been quarter, while an associative part is interposed.17 The ante- observed, but this is not a specific characteristic of dystonia rior GPi has been targeted in patients affected by Tourette as a similar abnormality is found in other basal ganglia syndrome, characterized by motor and vocal tics,18 and diseases. Maybe, the coexistence of reduced intracortical also in Lesch-Nyan syndrome, on which self-mutilation is inhibition and an injury to basal ganglia, which can lead to coupled with spasticity, dystonia, and other symptoms.4 a decreased inhibition of thalamic activity and conse- The VPL sensorimotor GPi, the so-called Laitinen and quently to an increased excitability of the motor cortex, Leksell target, has been recognized as the optimal site for can cause clinical expression of dystonia. Data recorded lesional surgery and DBS in Parkinson disease and in from GPi in our four patients show a mean firing rate of patients with dystonia. Choice of target position for 35Hz, similar to those found in other series.24 electrode insertion in DBS for children has been described, Vitek et al.21 have postulated that pallidotomy may work at the junction of the anterior two-thirds and posterior- by interrupting an unregulated and disruptive circuit, third of the GPi In adults the target region is most allowing the remaining structures and circuits to function commonly documented as the posteroventeral GPi.19 more normally. Neuromodulation of a more anterior part of GPi proved effective in DYT1 positive patients, who received a bilateral STUDY LIMITATIONS GPi-DBS with two electrodes implanted in each nucleus In this work, sample size is relatively small; this limitation after efficacy reduction of the lead on VPL.20 is because of the low incidence of status dystonicus. Fur- In our series pallidotomy resulted in the mid portion of ther multicentric investigations will be required to confirm the GPi which represents the motor part of the GPi. This the efficacy of the described technique. targeting allows for obtaining benefit on dystonic Another source of weakness of this study should be the symptoms, without preventing patients from receiving a relatively short follow-up; however, we consider our further gain from subsequent neuromodulation of the most outcome as a good result if we compare it with literature posterior part (VPL) of the GPi. Considering the staged data on outcome of status dystonicus after pallidotomy and implantation of multiple electrodes at the level of GPi,21 it other surgical approaches.

Pallidotomy in Status Dystonicus Carlo Efisio Marras et al. 655 CONCLUSION ACKNOWLEDGEMENTS Our results confirm the efficacy of the bilateral mid lesion- We thank Enrica and Fergal O’ Reilly for their support in manu- ing of GPi in treating pediatric patients affected by sec- script revision. The authors have stated that they had no interests ondary dystonia complicated by status dystonicus. that might be perceived as posing a conflict or bias.

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